This randomized phase II trial studies how well two doses of carfilzomib work with dexamethasone in treating patients with relapsed or refractory multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with dexamethasone may kill more cancer cells. This study is looking to see if giving a higher or lower dose of carfilzomib with dexamethasone is more beneficial than the other.

Progression Free Survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]

Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test.

Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that cycle 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II.

Drug: dexamethasone

given IV

Other Name: decadron

Drug: carfilzomib

given IV

Other Names:

kyprolis

PR-171

Experimental: Arm II (dexamethasone, high-dose carfilzomib)

Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that cycle 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: dexamethasone

given IV

Other Name: decadron

Drug: carfilzomib

given IV

Other Names:

kyprolis

PR-171

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate and compare progression free survival (PFS) of two different doses of carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or refractory disease.

SECONDARY OBJECTIVES:

I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates (RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high dose carfilzomib.

III. To evaluate the safety of this combination for this patient population. IV. To evaluate overall survival (OS).

Note that for the first course of treatment on both arms carfilzomib is given at a reduced rate to assess toxicity.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years from initial registration.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

REGISTRATION STEP 1: INITIAL RANDOMIZATION

Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be relapsed or refractory; all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma

Patients must have measurable disease within 28 days prior to registration

Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 28 days prior to registration; for study purposes, a regimen is defined as follows:

An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden

Any maintenance therapy used after an Induction should be considered part of that Induction regimen

Use of any agent or combination of agents more than once during the patient's disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens)

Patients must not be receiving any other concurrent therapy considered to be investigational; patients must not be planning to receive any radiotherapy (except localized radiation for palliative care); patients must not be planning to receive any concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative intent

Patients must have complete history and physical examination within 28 days prior to registration

Patients must have baseline PET scan within 28 days prior to registration; note that images are submitted centrally for review

Patients with non-secretory MM or known primary amyloidosis are not eligible

Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% within 14 days prior to registration

Patients who are HIV+ and do not meet all of these criteria are not eligible for this study

Patients with known hepatitis B or hepatitis C infection must have viral load < 800,000 IU/L within 28 days prior to registration

Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration

Patients must be off myelosuppressive chemotherapy and non-myelosuppressive chemotherapy and external beam radiation therapy (XRT) for >= 28 days (>= 6 weeks for nitrosoureas) and must have recovered to =< grade 1 from all treatment associated toxicities prior to registration; patients are allowed to have treatment for up to 7 days with pulse steroids for a myeloma-related complication prior to registration, as considered necessary by the treating physician

Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted

Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

REGISTRATION STEP 2: CROSSOVER

Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib) and progressed prior to completing 12 cycles of protocol therapy

At least 14 days and no more than 28 days must have elapsed between the last day of treatment on Arm 1 and registration to Arm 3

Patients must have recovered from all non-hematologic toxicities to =< grade 2 and from all hematologic toxicities to =< grade 3 prior to registration

Patients must have been able to complete their last treatment cycle prior to progression at the full assigned dose (i.e. no dose reduction for toxicity)

Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurements

Patients must not have ejection fraction decrease > 10% from baseline (as determined by ECHO) or other ejection fraction decrease accompanied by other clinical signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure, measured within 28 days prior to registration; if any question exists regarding individual patient eligibility in this situation, contact the study coordinator for determination

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01903811